Endogenous stimulus-powered antibiotic release from nanoreactors for a combination therapy of bacterial infections

Endogenous stimulus instead of external intervention for targeted delivery and controlled release represents a key challenge in nanomedicine research. Through rational design, here we report the cascade nanoreactors for bacterial toxin targeted and gas triggered antibiotic release by wrapping calcium peroxide (CaO2) as reactor fuel element. Once encountering pathogenic bacteria in vivo, these nanoreactors serve to anchor the toxins without compromising their structural integrity, and these toxins pierce nanoreactors to form pores, through which water molecules enter the nanoreactors to react with CaO2 and produce hydrogen peroxide (H2O2). Meanwhile, partial H2O2 decomposes to oxygen as the power to drive the drug release in nanoreactors, which stimulate the body's immune response after capturing bacterial toxins and significantly reduce the toxicity of toxins, thereby improving the therapeutic effect of bacterially infected mice. This strategy provides a Domino Effect approach for treating infections caused by bacteria that secrete pore-forming toxins.